Fifty to seven-five percent of RBC components from donors with sickle cell trait occlude leukocyte reduction filters. People with sickle cell trait are healthy, but very low oxygen levels, low pH, and high hemoglobin concentrations can induce RBC intracellular hemoglobin S polymerization. We have found that hemoglobin S polymerization due to low oxygen tension in venous blood and low ph and high osmolarity of the citrate anticoagulant is responsible for the failure of RBC components from donors with sickle cell trait to filter. The goal of these studies is to develop a practical method to allow the successful leukocyte reduction by filtration of all RBC components collect from donor with sickle cell trait. The method should be easy to use in conjunction with existing blood collection technologies. We have shown that increasing the oxygen tension in sickle cell trait RBC components allows effective leukocyte reduction with a filter designed to remove leukocytes from RBCs. However, standard filters must be used with RBC components that are less than 24 hours old. To increase oxygen levels within 24 hour to levels sufficient to allow effective filtration, blood must be stored in gas permeable bags and agitated. Since it is likely that blood collection centers would have to document that rocking does not damage the RBCs, agitation is not practical for transfused blood. Alternatively, air can be added to blood storage bags to increase oxygen levels and allow effective filtration, however, it is not practical for blood collection centers to add air sterilely to blood components. We hypothesized that it would be possible to increase oxygen levels in sickle cell trait donor blood to sufficient levels to permit successful filtration without agitation by storage in gas permeable bags with a larger than normal surface to volume ratio and for a longer storage duration prior to filtration. At least one leukocyte reduction filter is available that can be used to remove leukocytes from blood stored up to 72 hours. When blood was filtered fresh it occluded these filters, but when it was stored 3 days in large capacity bags made from oxygen permeable material suitable for whole blood storage, CLX, oxygen tensions increased to levels high enough to allow effective leukocyte reduction by filtration.